Gain of 1q Is Associated with Adverse Outcome in Favorable Histology Wilms’ Tumors

Abstract

Although several genes/genetic loci involved in the etiology of Wilms' tumor have been identified, little is known of the molecular changes associated with relapse. We therefore undertook an analysis by comparative genomic hybridization (CGH) of 58 tumor samples of favorable histology Wilms' tumor taken at initial diagnosis and/or relapse. Tumors with anaplastic histology were excluded as this is known to be associated with p53 mutation and a poor prognosis. A control group of 21 Wilms' tumors that did not relapse was also analyzed. The overall frequency of gains or losses of genetic material detected by CGH was similar in both groups (77% in relapsing tumors and 70% in the nonrelapse group) as was the median number of changes per tumor (relapse group: n = 4, range, 1 to 19; nonrelapse group: n = 3, range, 1 to 8). However, gain of 1q was significantly more frequent in the relapse series [27 of 46 (59%) versus 5 of 21 (24%), P: = 0.019]. In 12 matched tumor pairs, the CGH profiles, including 1q gain, were similar at diagnosis and relapse, with little evidence for further copy number changes being involved in clonal evolution. The results suggest that 1q gain at diagnosis could be used to identify patients with favorable histology Wilms' tumor at increased risk of relapse who might benefit from early treatment intensification.

Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene

“…A loss of 1q was also detected in about 15% of papillary RCCs (Jiang et al, 1998;Reutzel et al, 2001) and in less than 10% of clear cell RCCs . In Wilms tumors, 1q gain was described to be a predominant alteration in comparative genomic hybridization analyses (Hing et al, 2001). Interestingly, LOH at loci 1q21-22 and 1q32 has been also associated with tumor adverse outcome (Law et al, 1997;Natrajan et al, 2006).…”

Pediatric Ependymoma: Biological Perspectives

“…1 and 3), justifying its further assessment as a prognostic marker in children. The gain of chromosome 1q is associated with an unfavorable outcome in Wilms' tumors, neuroblastomas, and Ewing's sarcomas, which suggests a generic role in pediatric tumor progression and recurrence (143)(144)(145). Conventional cytogenetics suggests that 1q gain results from a variety of unbalanced rearrangements with material from numerous partner chromosomes rather than a single, recurrent translocation (43,44).…”

Current Therapy for Wilms’ Tumor

“…Future Children's Oncology Group (COG) clinical studies will augment therapy for patients with favorable histology Wilms' tumor and LOH at 1p and 16q. Other promising prognostic markers are an increase in gene copy number or expression at chromosome 1q [28,29] and telomerase expression level [30,31]. Gene expression profiling also shows promise to identify new prognostic factors [32][33][34].…”